Preparation and in vitro evaluation of hot-melt extruded pectin-based pellets containing ketoprofen for colon targeting
This work developed high drug-load pellets for colon targeting in minimal steps by coupling hot-melt extrusion (HME) with a die-surface cutting pelletizer, offering a potential continuous pellet manufacturing process. Ketoprofen (KTP) was selected as a model drug for this study due to its thermal stability and severe upper gastrointestinal side effects. Low and high methoxyl grade pectins were the enzyme-triggered release matrix, and hydroxypropyl methylcellulose (HME 4 M/HME 100LV) was used as a premature release-retarding agent. The powder X-ray diffraction technique and the differential scanning calorimetry results revealed that KTP exists in the solid-solution state within the polymeric matrix after the HME step.
Highlights
- Enzyme-triggered colon drug delivery approach with hot-melt extrusion.
- Low and high methoxyl grade pectins-based matrix for colon targeting.
- Hydroxypropyl methylcellulose (HME 4 M and HME 100LV) as a premature release-retarding agent.
The scanning electron micrographs of the fabricated pellets showed a smooth surface without any cracks. The lead formulation showed the lowest premature drug release (∼13%) with an extended KTP release profile over a 24 h period in the presence and absence of the release-triggering enzyme. The lead formulation was stable for 3 months at accelerated stability conditions (40 °C/75 ± 5% RH) concerning drug content, in vitro release, and thermal characteristics. In summary, coupling HME and pelletization processes could be a promising technology for developing colon-targeted drug delivery systems.
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Materials
KTP was purchased from PCCA (Houston, TX, USA) (Lot No. C171492). Genu® pectin type D slow set-Z (High methoxyl grade; Pectin HM) (Batch: GR10002240) and Genu® pectin type LM-104 AS-FS (Low methoxyl grade; Pectin LM) (Batch: SK30015244) were purchased from CPKelco Company (Atlanta, GA, USA). AFFINISOL™ HPMC HME 4 M (4 M) (Lot No. INR524352) and HME 100LV (100LV) (Lot No. INR524351) were kind gifts from Colorcon Inc. (West Point, PA, USA). Pectinex® Ultra SP-L (3300 PGNU/g activity) was purchased from Modernist Pantry LLC (Eliot, ME, USA). Transparent hard gelatin capsule shells, size 00 were purchased from Total Pharmacy Supply Company (Arlington, TX, USA). Acetonitrile and methanol solvents were of High-Performance Liquid Chromatography (HPLC) and purchased from ThermoFisher Scientific (Waltham, MA, USA).
Sagar Narala, Dinesh Nyavanandi, Preethi Mandati, Ahmed Adel Ali Youssef, Abdullah Alzahrani, Praveen Kolimi, Feng Zhang, Michael Repka, Preparation and in vitro evaluation of hot-melt extruded pectin-based pellets containing ketoprofen for colon targeting, International Journal of Pharmaceutics: X, Volume 5, 2023, 100156, ISSN 2590-1567, https://doi.org/10.1016/j.ijpx.2022.100156.